0000000000017674

AUTHOR

Rana S. Moubarak

Epigenetic Silencing of CDR1as Drives IGF2BP3-Mediated Melanoma Invasion and Metastasis.

Summary Metastasis is the primary cause of death of cancer patients. Dissecting mechanisms governing metastatic spread may uncover important tumor biology and/or yield promising therapeutic insights. Here, we investigated the role of circular RNAs (circRNA) in metastasis, using melanoma as a model aggressive tumor. We identified silencing of cerebellar degeneration-related 1 antisense (CDR1as), a regulator of miR-7, as a hallmark of melanoma progression. CDR1as depletion results from epigenetic silencing of LINC00632, its originating long non-coding RNA (lncRNA) and promotes invasion in vitro and metastasis in vivo through a miR-7-independent, IGF2BP3-mediated mechanism. Moreover, CDR1as le…

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Abstract PR04: Epigenetic silencing of CDR1as drives IGF2BP3-mediated melanoma invasion and metastasis

Abstract Metastasis is the primary cause of death of cancer patients. Dissecting mechanisms governing metastatic spread may uncover new biology and/or yield promising therapeutic insights. Here we investigated the role of circular RNAs (circRNAs), a class of noncoding RNAs lacking characterized functions, in metastasis, using melanoma as a model aggressive tumor. We analyzed RNA-seq of melanocytes and melanoma short-term cultures to characterize the landscape of circRNA in melanocytic cells. We observed silencing of Cerebellar Degeneration Related 1 (CDR1as), a neuronal-enriched circRNA and known regulator of the microRNA miR-7, in melanoma cell lines and short-term cultures compared to cul…

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BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways.

Neuroblastoma (NB) is a neoplasm of the sympathetic nervous system, and is the most common solid tumor of infancy. NBs are very heterogeneous, with a clinical course ranging from spontaneous regression to resistance to all current forms of treatment. High-risk patients need intense chemotherapy, and only 30-40% will be cured. Relapsed or metastatic tumors acquire multi-drug resistance, raising the need for alternative treatments. Owing to the diverse mechanisms that are responsible of NB chemoresistance, we aimed to target epigenetic factors that control multiple pathways to bypass therapy resistance. We found that the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromat…

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